Alzheimer's May Be Diabetes-Like Illness

Rats without insulin in brain developed symptoms, researchers report

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By Steven Reinberg
HealthDay Reporter

FRIDAY, March 24, 2006 (HealthDay News) -- Giving more weight to the notion that Alzheimer's may be a diabetes-like disease, researchers say rats depleted of insulin in the brain went on to develop an Alzheimer's-like illness.

By depleting insulin and its related proteins in the rodent's brains, the researchers say they have been able to replicate the progression of Alzheimer's disease. This included amyloid plaque deposits, neurofibrillary "tangles," impaired cognitive functioning, cell loss, and overall brain deterioration. All of these are characteristic of Alzheimer's disease.

"True Alzheimer's disease is a kind of insulin resistance in the brain," concluded lead researcher Dr. Suzanne M. de la Monte, a neuropathologist at Rhode Island Hospital and a professor of pathology and clinical neuroscience at Brown Medical School, in Providence, R.I.

She called the study "very exciting," adding that it "leads to new concepts of how to treat the disease."

According to the researchers, the study demonstrates that Alzheimer's is a brain-specific disorder, distinct from other types of diabetes, such as the inherited form, type 1, and obesity-linked type 2. "This study shows that Alzheimer's is a [new] type of diabetes," de la Monte said. "It's type 3 diabetes."

Other experts remained unconvinced, however.

"To date, the construct that Alzheimer's is type 3 diabetes remains largely unsupported," said Dr. Sam Gandy, chairman of the Medical and Scientific Advisory Council at the Alzheimer's Association and director of the Farber Institute for Neurosciences at Thomas Jefferson University, Philadelphia.

The report appears in the March issue of the Journal of Alzheimer's Disease.

According to de la Monte, a loss of insulin in the brain may trigger Alzheimer's onset because brain cells need insulin to function and survive. When this happens, oxidative stress increases, the brain deteriorates, and there is loss of cognitive function, plus a buildup of plaques and tangles in the brain, she said.

Whether restoring insulin to the brain can slow or reverse the progression of Alzheimer's is something that de la Monte's team is looking at now in animals. "The results are under review," she said.

"We are looking at a brain form of diabetes," de la Monte said. "One can look forward to approaches that may work in the brain which we already have available, or that might be modified to treat patients with neurodegeneration," she said.

De la Monte is convinced that what doctors call Alzheimer's is really several different conditions under one umbrella. "We will have to develop ways to be certain who has what kind of neurodegeneration," she said.

About 50 percent of patients diagnosed with dementia have Alzheimer's, de la Monte noted. "The others have a mixed condition or something else wrong with them," she said.

"There are a number of conditions that people call Alzheimer's disease," de la Monte said. "People are developing ways of testing insulin resistance in the brain, which will be necessary to validate any therapy that comes out of this."

However, one expert doesn't think that her team has yet made a convincing case for the theory.

"The paper overreaches," said Gandy.

He noted that de la Monte's group injected the rats' brains with Streptozotocin, the compound they used to inhibit local insulin production. So, it's not clear whether the brain changes her group noted were related to a lack of insulin, or this insult to the brain. "Streptozotocin, which causes oxidative stress, would be predicted to cause such stress in many tissues, including the brain," Gandy said.

In addition, changes the researchers observed in the brains of the mice were only modest, with no clear structural pathology evident, he said.

Another expert believes insulin's role in Alzheimer's may only be part of the picture.

"There is definitely speculation that insulin is linked to Alzheimer's," said Dr. Zoe Arvanitakis, an assistant professor of neurological sciences at Rush University Medical Center, in Chicago.

"But given the complexity of the illness, it is probably unlikely that addressing a single mechanism of illness, for example giving insulin, is probably unlikely to cure the disease," Arvanitakis said. "It might help some people. It might help to some extent. But it is unlikely that a single approach will be the answer to the problem," she said.

More information

For more on Alzheimer's disease, head to the Alzheimer's Association.

SOURCES: Suzanne M. de la Monte, M.D., M.P.H, neuropathologist, Rhode Island Hospital, professor, pathology and clinical neuroscience, Brown Medical School, Providence; Sam Gandy, M.D., Ph.D., chairman, Medical and Scientific Advisory Council, Alzheimer's Association, and director, Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia; Zoe Arvanitakis, M.D., assistant professor, neurological sciences, Rush University Medical Center, Chicago; March 2006 Journal of Alzheimer's Disease

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